Arf6 Acts through FilGAP to Down-regulate Rac and Regulates Plasma Membrane Blebbing [Signal Transduction]

February 13th, 2014 by Kawaguchi, K., Saito, K., Asami, H., Ohta, Y.

The small GTP-binding protein Arf6 reorganizes actin cytoskeleton through the regulation of Rac activity. We identified FilGAP, a Rac specific Rho GTPase-activating protein that is recruited to plasma membranes by binding to activated Arf6. FilGAP binds to Arf6 through its pleckstrin-homology (PH) domain. Activated Arf6 stimulated RacGAP activity of FilGAP and knockdown of endogenous Arf6 by small interference RNA (siRNA) suppresses FilGAP-mediated bleb formation. Mutant FilGAP lacking PIP3-binding (FilGAP R39C) binds to activated Arf6 and induces bleb formation. Moreover, bleb formation induced by wild-type FilGAP occurs in the presence of PI3 kinase inhibitors, suggesting PIP3-independent interaction between FilGAP and Arf6. We propose that FilGAP may function as a mediator of the regulation of Rac by Arf6.